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TIPs - using viruses for treatment

  • [Leor Weinberger: Can we create vaccines that mutate and spread? TED Talk](https://www.ted.com/talks/leor_weinberger_can_we_create_vaccines_that_mutate_and_spread?language=en#t-798841)
    • viruses mutate, our drugs don’t
    • adherence / deployment - hard to give certain the drugs
    • idea: uses viruses as treatment
      • than superspreaders will spread treatment to others
      • replaces hiv instruction set with amputated instruction set which is not harmful
      • “therapeutic interfering particles” or “TIPs” are engineered deletion mutants designed to piggyback on a virus and deprive the virus of replication material


  • overview
    • age-associated - tons of people get it
    • doesn’t kill you, secondary complications like pneumonia will kill you
    • rate is going up
    • very expensive to treat
  • declarative memories are affected by Alzheimer’s
    • these are memories that you know
  • first 2 areas to go in Alzheimer’s
    1. hippocampus
      • patient HM had no hippocampus
        • no anterograde memory - learning new things
      • hippocampus stores 1 day of info
        • offloading occurs during sleep (REM sleep) to prefrontal cortex, temporal lobe, V4
        • dreaming - might see images as you are offloading
    2. basal forebrain - spread synapses all over cortex
      • uses Ach
      • ignition key for entire cortex
  • alzheimer’s characteristics only found in autopsy
    • amyloid plaques
      • maybe A-beta causes it
      • A-beta comes from APP
      • A-beta42 binds to itself
        • prion (starts making more of itself)
        • this cycle could be exacerbated by injury
        • clumps and attracts immune system which kills local important cells
          • this could cause Alzheimer’s
        • rare genetic mutations in A-beta increase probability you get Alzheimer’s
        • anti-inflammation may be too late
        • can take drugs that increase Ach functions - ex. cholinergic agonists, cholinesterase inhibitors
    • tangles
      • tangles made of protein called Tau
    • most people think these are just dead cells resulting from Alzheimer’s but some think they cause it


  • loss of substantia nigra pars compacta dopaminergic neurons
    • when you get down to 20% what you were born with
    • dopaminergic neurons form melanin = dark color
    • hits to head can give inflammation
  • know what they need to do - don’t have enough dopamine to act
  • treat with L Dopa -> something like dopamine -> take out globus pallidus
  • Lewy bodies are clumps of alpha synuclein - appear at dopaminergic synapses
    • clumps like A-beta42
    • associated with early-onset Parkinson’s (rare) associated with genetic mutations
  • bradykinesia - slowness of movement
  • age can give parksinson’s
  • no evidence that toxins can induce parkinsons
  • PTP/ pesticides can induce Parkinson’s in test animals
  • 1/500 people